The impact that diabetes has on the health of Americans is staggering. According to the American Diabetes Association in 2006 approximately 20.8 million Americans were diagnosed with diabetes. The cost of diabetes in 2002 was estimated at $132 billion. The number of deaths in 2006 attributed to complications associated with diabetes was estimated at 613 Americans per day.
New and improved systems and methods for treating and detecting diabetes are in high demand. Analytical biosensors provide one type of system that can be used to manage diabetes. Analytical biosensors have been embraced during the last decade as a means of combining the advantages of electrochemical signal transduction with the specificity inherent in biological interactions. For example, the use of continuous glucose monitoring (CGM) to manage diabetes is becoming increasingly popular.
Despite recent improvements in analytical biosensor systems, the available systems suffer from disadvantages. For example, systems employing a hydrogel sensor typically have short shelf lives and may leak sensor materials onto the skin of a user. Alternatively, bacterial growth or growth of other microorganism can contaminate or foul the biosensor rendering its measurements of analytes unreliable. In some instances, proteins, carbohydrates, cells, or fragments of cells from the user can bind to the sensor and interfere with measurements. Such binding can also contaminate the biosensor.
Membranes, films or other physical barriers have been used on the surface of sensor electrodes to impede contaminants from reaching the face of the electrode. Typical films which have been employed include cellulose acetate, poly(o-phenylenediamine), polyphenol, polypyrrole, polycarbonate, and NAFION®, i.e. tetrafluoroethylene-perfluoro-3,6-dioxa-4-methyl-7-octenesulfonic acid copolymer (E.I. du Pont de Nemours & Co., Wilmington, Del.). However, these membranes can be difficult to prepare and may not efficiently attach to the reactive surface of the electrode.
Some CGM systems require pretreatment of the skin with a hydrating formulation prior to attachment of the system. For example, with existing biosensor systems, a 10-40 minute skin hydration procedure is typically applied to the target skin site after treatment to increase skin porosity and before sensor application. The hydration procedure results in better sensor performance than is achieved without pretreatment (sensor signal follows well to reference blood glucose reading). Although it enables improved sensor performance, the skin hydration procedure requires undesirable labor, materials and time which may further complicate the procedure for device installation, and hence the cost of the system. Systems that do not require complicated or time consuming skin pretreatment procedures are desirable.
In still other CGM systems, a standard reference glucose method is used to calibrate the glucose sensor and then the sensor reports subsequent glucose readings based on the calibrated electrical signal. In principle, the blood glucose concentration of a test subject should be proportional to the measured electrical signal. For sensors based on the enzymatic conversion of glucose, for example where the enzyme glucose oxidase (GOx) utilizes water and oxygen to convert glucose into hydrogen peroxide (H2O2) and glucolactone, the enzymatic conversion is limited by the amount of available oxygen. When the supply of oxygen is limited, such as in interstitial fluid, the concentration of glucose exceeds the concentration of oxygen, the enzymatic conversion of glucose will be dependent on the oxygen supply, resulting in unreliable sensor glucose reading and hence affecting the sensor performance.
Various methods have been reported to mitigate the issue of oxygen limitation. Tierney et al. describes using reverse iontophoresis to limit glucose extraction, maintaining desirable oxygen to glucose balance (M. Tierney et al., Annals of Medicine, 32(9):632-641 (2000)). U.S. Pat. No. 7,110,803 to Shults et al. discloses using a glucose-limiting membrane layer that has a high oxygen to glucose permeability ratio. U.S. Pat. No. 7,108,778 to Simpson et al. discloses using an auxiliary electrode to generate oxygen for the sensing chemistry. However, each of these methods requires the addition of extra elements to the CGM system, thereby increasing the cost and complexity of the system. A simple method for increasing the amount of available oxygen to the sensor without increasing the cost and complexity of the system is needed.
Therefore, it is an object of the invention to provide an improved transdermal analyte monitoring system.
It is another object to provide a method for reducing biofouling and/or contamination in a transdermal analyte monitoring system.
It is another object to provide methods for improving the accuracy of detection and/or quantification of an analyte by a transdermal analyte monitoring system.